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MR Vol.11 No.4 indexに戻る
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MODERN RHEUMATOLOGY
Vol.11 No.4 |
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Molecular diversity of the HLA-B27 gene
and its association with disease |
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| N. K. Mehra1, U. Kanga1 |
| (1)Department of Transplant Immunology and Immunogenetics,
All India Institute of Medical Sciences, Ansari Nagar, New Delhi
110029, India |
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| Abstract |
| Abstract The human major histocompatibility complex
(MHC) class I gene HLA-B27 bears a striking association with ankylosing
spondylitis and related spondyloarthropathies. This association transcends
all ethnic and geographical boundaries. The primary function of HLA-B27
as an MHC class I protein is to form a complex with #2-microglobulin
resulting in a structure that is capable of presenting short antigenic
peptides for recognition by cytotoxic T lymphocytes. HLA-B27 represents
a family of 23 closely related alleles (B*2701-23) called subtypes
of HLA-B27, most of which have evolved from B*2705. Studies from
different parts of the world reveal differences in the population
distribution. HLA-B27 subtypes are characterized by nucleotide substitutions
(mostly nonsynonymous) in exons 2 and 3 which encode !1 and !2 domains
of the peptide binding groove respectively. Gene conversion, point
mutation, genetic draft, and recombination events are various mechanisms
leading to heterogeneity of HLA-B27 and its evolution. Clustering
of differences in the C/F pockets of HLA-B27 influences the peptide
binding. Thus variations in strength of disease association of various
HLA-B27 subtypes may be due to differences in peptide interaction
of HLA-B27 subtypes. Because the association between HLA-B27 and
disease is not absolute, possible influence of other genes on disease
susceptibility needs further investigation. In this regard, the role
of several candidate genes that include non-B27 MHC genes, MHC-related
genes, MHC genes involved in antigen processing and transplant, cytokine
genes, and markers on other chromosomes may be important. Besides
these significant developments, satisfactory answers to many unresolved
issues are sought. Understanding the exact mechanism of the HLA-B27
and disease association is continuing to be a subject of many studies. |
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| Key words |
| Key words Asian Indians ・ B27 heterogeneity
・ Disease-associated alleles ・ Peptide binding ・ Population differences |
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